PROJECT SUMMARY/ABSTRACT The NYU Women?s Health Study (NYUWHS) is a prospective cohort study of 14,274 healthy women who were enrolled in 1985-1991. In addition to data on reproductive factors, medical history and lifestyle, the study collected serum samples from all participants at enrollment. Serum samples were also collected at subsequent breast cancer screening visits from over half the women. DNA is available for all study participants. The NYUWHS has initiated or participated in studies of cancer of the breast, endometrium, ovary, colorectum, lung, pancreas, kidney, liver, brain, and non-Hodgkin lymphoma (NHL). Exposures studied include diet, reproductive factors, and circulating levels of hormones, dietary markers, cytokines, and other biomarkers. The overall goal of the study is to understand the etiology of cancer and provide information that can lead to prevention. The objectives of this application are to maintain and enhance the infrastructure of the study over the next five years. The specific aims are to: 1) Continue cancer case ascertainment; 2) Continue to maintain the complex database; 3) Continue to maintain the biorepository of blood samples (serum, cell precipitates, and clots) and tumor tissues; 4) Facilitate collaborations and data sharing through maintenance of the study website and timely response to requests; 5) Continue tumor tissue collection for major cancer sites (breast, colorectal, endometrial, and lung) and, for breast cancer, construction of tumor microarrays for classification in molecular subtypes; 6) Expand the biorepository by collecting a stool sample from approximately 3,400 women; 7) Assess the long-term reproducibility of new potential cancer biomarkers. As of 1/1/2016, 5,047 incident cancers have been identified and the continued follow-up is expected to identify an additional 1,277 cancer cases (total = 5989). The specific strengths of the NYUWHS include: 1) Long follow-up: NYUWHS participants have been followed- up for 27 to 33 years, and the impact of changes in risk factors over time in relation to cancer risk can therefore be examined. 2) Serum collected at enrollment and DNA are available for all participants, making the biorepository a valuable resource to study associations between genetic variation, biomarkers, and cancer risk; 3) Repeat serum samples, which can be used to assess temporal reliability of circulating markers, are available for over half of the participants; 4) While the majority of large Cancer Epidemiology Cohorts started enrollment at age 50, 6,659 NYUWHS participants (47%) were between the ages of 35 and 49 at enrollment/blood donation, providing opportunities for the study of risk factors and biomarkers measured in younger women.